Aromatic aldehyde compounds are useful for making numerous other compounds, as well as for their own properties. For example, in Method A shown in the description below an aldehyde undergoes chemical reactions to form a compound which is a cPLA2 inhibitor having a variety of therapeutic uses, as described below. It is often necessary or desirable to obtain such an aldehyde from a corresponding dihalogenated aromatic compound.
Certain methods for converting a dihalogenated aromatic compound to its corresponding aldehyde are known. Typically, they require harsh reaction conditions, which generally involve high temperatures and as a strong acid, such as concentrated sulfuric acid, or a strong base, such as aqueous sodium hydroxide. Examples of these methods are found in Chung and Kim, Tetrahedron, 1995, 51(46), 12549–12562, and Goodman, et al., J. Am. Chem. Soc., 1995, 117, 8447–8455.
Conversion of dihalo aromatics to aldehydes has been shown to occur by reaction with sodium carbonate (Adediran, et al., Bioorg. Med. Chem., 2001, 42, 1175–1183), and with sodium bicarbonate (Langer, et al., Bioorg. Med. Chem., 2001, 9, 677–694), with heavy metal salts like silver nitrate (Semmelhack, et al., J. Am. Chem. Soc. 1994, 116, 7108).
It has been reported that benzal bromides may be hydrolyzed to the corresponding benzaldehyde using potassium carbonate in dimethylsulfoxide (DMSO) solvent (Huaping Xi, et al., J. Org. Chem., 1999, 64(29), 9286–9288). In this reaction, the potassium carbonate hydrolyzed the dibromo compounds to the corresponding aldehydes.
Harsh reaction conditions are not suitable for all dihalogenated aromatics because undesirable side reactions may occur. Furthermore, it is safer and less expensive to avoid using strong acids and bases and high temperatures. Although mild reaction conditions have been reported, development of good procedures for such transformation is desirable.
Sulfoxides are often used as an oxygen-donating agent in organic synthesis, for example, to convert structurally diverse alcohols to their corresponding carbonyl compounds in the presence of activating reagents, such as transition metal catalysts (Steinhoff, et al., J. Amer. Chem. Soc., 2002, 124(5), 766–767; Arterburn and Perry, Org. Lett., 1999, 1(5), 769–771.), or dicyclohexylcarbodiimide (Pfitzner and Moffatt, J. Amer. Chem. Soc., 1965, 87(24), 5661–5670). Activation is necessary for the sulfoxide to effect the desired transformation.